1. ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and St Thomas' NHS Foundation Trust, London, UK 3 Barts and The London NHS Trust, London, UK

2. Systolic BP Webb A. et al., Hypertension 2008;51:1-7 (23 mmol NO 3 - )

4. Hypothesis Provision of dietary nitrate may enhance glucose handling Aim To establish whether ingestion of a dietary nitrate load improves glucose handling as shown by pl. glucose response to 75 g GTT

5. Study criteria Healthy subjects aged 18-45 years BMI between 18 and 40 kg/m 2 Normotensive Not taking systemic medication other than OCP

6. Baseline data

7. Individual visit -2h Start -1h KCl or KNO3 (24 mmol) 0h 75 g GTT +1h+2h Finish Double blind randomised placebo controlled cross-over design KNO 3 v KCl (both 24 mmol, capsules) +Gaviscon NO 3 - (24 mmol) ≈ 500 ml beetroot juice* *Webb A. et al., Hypertension 2008;51:1-7

8. Effect of dietary nitrate on plasma NO 3 -, NO 2 - & exhaled NO

9. Effect of dietary nitrate on plasma glucose & insulin during GTT (n=8)

11. Effect of dietary nitrate on BP

12. New hypothesis Association between glucose response + BP response to nitrate; on exposure to nitrate, subjects may either: ‘respond’ = ↓ glucose ‘reactors’ = ↑ glucose & this determines the BP response to nitrate

13. New study – 20 participants Aim: To prospectively determine whether there is an association between the glucose response and the BP response to nitrate Similar protocol, Responders or reactors: >5% Δ AUC glucose, KNO 3 v KCl KNO 3 (8 mmol) ≈ 3-4 portions of green leafy veg Primary outcome: Difference in change in BP with nitrate, between nitrate reactors and responders (glucose)

14. Responders Reactors

20. Responders v Reactors

22. Summary & Conclusions BP ↓ by nitrate in reactors BP ↑ by nitrate in responders Responders have higher glucose curves in control: ↓ by nitrate (but BP ↑) Reactors have higher insulin curves with nitrate than responders – may be mechanism for vasodilatation and ↓BP

23. Acknowledgments Andrew Webb Joanne Hunt Sami Omar Tony Marinaki Lynette Fairbanks Gabriella Passacquale Kenneth Connell Henry Fok Ganesh Arunachalam Sikder Zubair Rahim Benyu Jiang Sally Brett Karen McNeill Albert Ferro Phil Chowienczyk Clinical Research Facility nursesKCL BHF Centre

25. Baseline data

26. Baseline data - Responders

27. Baseline data - Reactors

28. Baseline data – Responders >5% Δ AUC glucose

29. Baseline data - Reactors >5% Δ AUC glucose

30. Glucose

31. Insulin

32. C-peptide

33. Mean baseline SBP

34. Green leafy veg + diabetes increasing consumption of green leafy vegetables by one and a half UK portions a day (121.9g) could result in 14% reduction in the incidence of type 2 diabetes (Carter P. et al., BMJ 2010;341:c4229)

35. Responders v Reactors

37. Comparison of control glucose curves